Registration Dossier

Administrative data

Description of key information

With the value noted, DIPB is not toxic at doses higher than the limit for classification.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older study: meets scientific standards with acceptable restrictions (e.g. limited number of animals in study and partly limited documentation)
Qualifier:
no guideline followed
Guideline:
other: Study from 1976 (no guidelines available at the time the study was performed).
Deviations:
not applicable
Principles of method if other than guideline:
Mixed groups of 5 male and female Sprague-Dawley strain albino rats were dosed with undiluted TS via gavage at 4 dose levels. Observations were made for toxic signs and the viscera of the test animals were examined macroscopically.
GLP compliance:
no
Remarks:
Study from 1976 (GLP was not compulsory at the time the study was performed).
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Initial body weights: 220 - 235 g (m) and 225 - 240 g (f)
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
3160, 3980, 5010 or 6310 mg/kg bw
No. of animals per sex per dose:
mixed groups of 5 male and female rats
Control animals:
not specified
Details on study design:
Survivors were sacrificed 14 days after dosing.
Statistics:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 900 mg/kg bw
95% CL:
3 550 - 4 290
Mortality:
3160 mg/kg bw: 0/5
3980 mg/kg bw: 3/5
5010 mg/kg bw: 3/5
6310 mg/kg bw: 5/5

Survival time: 1 - 5 days, most deaths within 2 days.
Clinical signs:
reduced appetite and activity (1 - 3 days in survivors), increasing weakness, collapse and death.
Body weight:
No data
Gross pathology:
Decedents: Haemorrhagic areas of the lungs, liver discoloration and acute GI tract inflammation.
Survivors: viscera appeared normal.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 value for male and female rats was 3900 mg/kg bw.
Executive summary:

In this older study mixed groups of 5 male and female Sprague-Dawley strain albino rats were dosed via gavage with undiluted TS at doses of 3160, 3980, 5010 or 6310 mg/kg bw. The oral LD50 value for male and female rats was given with 3900 mg/kg bw. Toxic signs included reduced appetite and activity, increasing weakness, collapse and death. In decedents, haemorrhagic areas of the lungs, liver discoloration and acute GI tract inflammation were noted, while in survivors viscera appeared normal.

As the other data indicated a LD50 higher than this one, it will be taken as the oral LD50 for mix DIPB

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 900 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older study: meets scientific standards with acceptable restrictions (e.g. partly limited documentation)
Qualifier:
no guideline followed
Guideline:
other: Study from 1976 (no guidelines available at the time the study was performed).
Deviations:
not applicable
Principles of method if other than guideline:
6 male SD rats were exposed (whole body) to 2100 mg TS/m3
GLP compliance:
no
Remarks:
Study from 1976 (GLP was not compulsory at the time the study was performed).
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
No further data
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
other: air
Details on inhalation exposure:
Initial sample: 107.2 g
Recovered sample: 104.1 g
Condensed sample: 0.0 g
Vaporised sample: 3.1 g
Chamber temperature: 25 degrees C
Chamber humidity: 80 %
Chamber volume: 35 L
Air flow rate: 4.0 L/min
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
2100 mg/m3
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
Initial sample: 107.2 g
Recovered sample: 104.1 g
Condensed sample: 0.0 g
Vaporised sample: 3.1 g
Chamber temperature: 25 degrees C
Chamber humidity: 80 %
Chamber volume: 35 L
Air flow rate: 4.0 L/min
Statistics:
No data
Sex:
male
Dose descriptor:
LC50
Effect level:
> 2 100 mg/m³ air
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: LC0
Mortality:
0/6
Clinical signs:
other: None
Body weight:
No data
Gross pathology:
14 days: viscera appeared normal
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LC0 value for male rats was > 2100 mg/m3 for 6h exposure, which correspond to CL50 / 4h > 3,15 mg/kg. As for cumene (isopropylbenzene) the LC0 is > 5.5 mg/L mist it is anticipated that DIPB LC50 is >5 mg/kg mist.
Executive summary:

In this older study 6 male Sprague-Dawley strain albino rats were exposed to 2100 mg TS/m3 (whole body) over 6 hrs. None of the animals died and the viscera appeared normal 14 days after dosing. This correspond to CL0 / 4h > 3,15 mg/kg and certainly to a CL50 > 5 mg/L mist with dermal exposure.

There are 2 studies with DIPB and Cumene, indicating LC0 respectively at 2100 mg/m3 (6h) and 17600 mg/m3 (1h), while they have vapour pressure of 0.34 and 4.9 hPa. We do not know really if they are based on saturating Vps, anyway needing to heat the substance which will condensate to aerosol when reaching the rat whole exposure cages. We can estimate the 4 hours value with the Haber law, either with C.t=K or C3.T=K In the first case CL0 would be 3.15 and 5.18 mg/L respectively. In the second case the CL0 will be for DIPB and Cumene of 2.41 and 11.1 mg/L. From these data it is assumed that the CL50 of DIPB is > 5 mg/L aerosol, leading to no CLP classification.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5.5 mg/m³
Quality of whole database:
Old but sufficent with the supporting data. LC0 >3.15 and isopropylbenzene LC0 >5.5 mg/L. No effects een on animals

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Older study: meets scientific standards with acceptable restrictions (e.g. limited number of animals in study and partly limited documentation)
Qualifier:
no guideline followed
Guideline:
other: Study from 1976 (no guidelines available at the time the study was performed).
Deviations:
not applicable
Principles of method if other than guideline:
One or two New Zealand Albino rabbits (m or f) in each dosing group were dosed with undiluted TS over 24 hrs. Observations were made for toxic signs and the viscera of the test animals were examined macroscopically.
GLP compliance:
no
Remarks:
Study from 1976 (GLP was not compulsory at the time the study was performed).
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: New Zealand Albino
Sex:
male/female
Details on test animals and environmental conditions:
Initial body weights: 2100 - 2200 g (m) and 1800 - 2200 g (f)
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
No further data
Duration of exposure:
24 hrs
Doses:
1000, 2000, 3160, 5010 or 7940 mg/kg bw
No. of animals per sex per dose:
1000 mg/kg bw: 1 m
2000 mg/kg bw: 1 f
3160 mg/kg bw: 1 m
5010 mg/kg bw: 1 f
7940 mg/kg bw: 1 m / 1 f
Control animals:
not specified
Details on study design:
Survivors were sacrificed 14 days after dosing.
Statistics:
No data
Preliminary study:
Slighty irritating according to Draize socre: not irritating.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Mortality:
1000 mg/kg bw: 0/1 m
2000 mg/kg bw: 0/1 f
3160 mg/kg bw: 0/1 m
5010 mg/kg bw: 1/1 f
7940 mg/kg bw: 0/1 m and 1/1 f

Survival time: 2 - 4 days
Clinical signs:
reduced appetite and activity (4 - 7 days in survivors), increasing weakness, collapse and death.
Body weight:
No data
Gross pathology:
Decedents: Haemorrhagic areas of the lungs, liver hyperaemia, enlarged gall bladder and GI tract inflammation.
Survivors: viscera appeared normal.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value for male and female rabbits was > 3160 mg/kg bw.
Executive summary:

In this older study one or two New Zealand Albino rabbits (m or f) in each dosing group were dosed with undiluted TS at doses of 1000, 2000, 3160, 5010 or 7940 mg/kg bw over 24 hrs. Observations were made for toxic signs and the viscera of the test animals were examined macroscopically. The dermal LD50 value for male and female rabbits was given with > 3160 mg/kg bw. Toxic signs included reduced appetite and activity, increasing weakness, collapse and death. In decedents, haemorrhagic areas of the lungs, liver hyperaemia, enlarged gall bladder and GI tract inflammation were noted, while in survivors viscera appeared normal.

This is the lowest value, as the other study give a higher one (13700 mg/kg)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 160 mg/kg bw

Additional information

Oral:

In a study, mixed groups of 5 male and female Sprague-Dawley strain albino rats were dosed via gavage with undiluted TS at doses of 3160, 3980, 5010 or 6310 mg/kg bw. The oral LD50 value for male and female rats was given with 3900 mg/kg bw. Toxic signs included reduced appetite and activity, increasing weakness, collapse and death. In decedents, haemorrhagic areas of the lungs, liver discoloration and acute GI tract inflammation were noted, while in survivors viscera appeared normal.

Dermal:

In this study, one or two New Zealand Albino rabbits (m or f) in each dosing group were dosed with undiluted TS at doses of 1000, 2000, 3160, 5010 or 7940 mg/kg bw over 24 hrs. Observations were made for toxic signs and the viscera of the test animals were examined macroscopically. The dermal LD50 value for male and female rabbits was given with > 3160 mg/kg bw. Toxic signs included reduced appetite and activity, increasing weakness, collapse and death. In decedents, haemorrhagic areas of the lungs, liver hyperaemia, enlarged gall bladder and GI tract inflammation were noted, while in survivors viscera appeared normal.

Inhalation:

In this study 6 male Sprague-Dawley strain albino rats were exposed to 2100 mg TS/m3 (whole body) over 6 hrs. None of the animals died and the viscera appeared normal 14 days after dosing. This correspond to CL0 / 4h > 3,15 mg/kg and certainly to a CL50 > 5 mg/L mist with dermal exposure.

Justification for classification or non-classification

LD50 > 2000 mg/kg